What is the best course of action for a patient with HIV (Human Immunodeficiency Virus) and G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency who develops a pruritic maculopapular rash while taking sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis?

Best Course of Action: Switch to Atovaquone

For this patient with HIV, G6PD deficiency, and a severe hypersensitivity reaction to sulfamethoxazole/trimethoprim (including mucosal involvement), you should switch to atovaquone for PCP prophylaxis. 1, 2

Rationale for This Decision

Why This is a Severe Hypersensitivity Reaction

The clinical presentation indicates a serious drug reaction that mandates immediate discontinuation:

• Pruritic maculopapular rash covering trunk suggests a systemic hypersensitivity reaction 3
• Mucosal involvement (oral lesions) is a red flag for potential progression to severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome or toxic epidermal necrolysis 3
• Failure to respond to antihistamines (diphenhydramine) confirms this is not a simple allergic reaction 1

The FDA drug label explicitly warns that sulfamethoxazole/trimethoprim should be discontinued at the first appearance of skin rash, as it may be followed by more severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome 3. Continuing the medication or simply adding symptomatic treatment (options C and D) would be dangerous and potentially life-threatening. 3

Why NOT Dapsone (Option A)

Dapsone is absolutely contraindicated in this patient due to G6PD deficiency. 2, 4, 5

• The Annals of Oncology explicitly recommends checking G6PD levels before initiating dapsone due to the risk of hemolytic reactions in G6PD-deficient patients 2, 4
• Both dapsone alone and dapsone/pyrimethamine combinations can cause severe, potentially fatal hemolysis in G6PD-deficient individuals 5
• This is a well-established contraindication that cannot be overlooked 2, 4

Why Atovaquone is the Correct Choice (Option B)

Atovaquone is the safest and most appropriate alternative for this specific patient:

• Safe in G6PD deficiency: Unlike dapsone or primaquine-containing regimens, atovaquone does not cause hemolysis in G6PD-deficient patients 6, 5
• Effective for PCP prophylaxis: Guidelines from USPHS/IDSA recommend atovaquone as an alternative prophylactic agent when TMP-SMZ cannot be tolerated 1
• Proven efficacy: Atovaquone appears to be as effective as aerosolized pentamidine or dapsone for PCP prophylaxis 1
• Real-world evidence: Case reports demonstrate successful use of atovaquone in G6PD-deficient patients, even for severe PCP treatment 6

Why NOT Symptomatic Treatment Alone (Options C and D)

Adding loratadine (option C) or prednisone (option D) while continuing TMP-SMZ would be inappropriate:

• The presence of mucosal lesions suggests potential progression to life-threatening SCARs 3
• FDA labeling explicitly states that skin rash may be followed by more severe reactions and the drug should be discontinued 3
• Desensitization protocols mentioned in guidelines are only appropriate for non-life-threatening reactions without mucosal involvement, and should only be attempted after complete resolution of the reaction 1
• This patient's reaction is too severe for desensitization attempts 1, 3

Alternative Considerations

What About Clindamycin-Primaquine?

While clindamycin-primaquine is recommended as a preferred alternative for PCP treatment 2, 4, primaquine is also contraindicated in G6PD deficiency due to hemolytic risk 2, 4. This combination should not be used for this patient.

What About Aerosolized Pentamidine?

Aerosolized pentamidine is another guideline-recommended alternative 1, but:

• It is less convenient (requires nebulizer administration)
• It is less effective than atovaquone for systemic prophylaxis
• It does not provide cross-protection against toxoplasmosis (which this patient with CD4 <100 may need) 1

Critical Clinical Pearls

• Never continue TMP-SMZ when mucosal involvement is present - this is a harbinger of potentially fatal SCARs 3
• Always check G6PD status before prescribing dapsone or primaquine - hemolysis can be life-threatening 2, 4
• Atovaquone is more expensive but is the safest option in G6PD deficiency when TMP-SMZ fails 1, 6
• This patient needs continued PCP prophylaxis given CD4 count of 80 cells/mm³ - stopping prophylaxis is not an option 1

Answer: B) Switch to atovaquone